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An NADPH-independent mechanism enhances oxidative and nitrosative stress tolerance in yeast cells lacking glucose-6-phosphate dehydrogenase activity
Yeast ( IF 2.2 ) Pub Date : 2021-03-01 , DOI: 10.1002/yea.3558
Yuki Yoshikawa 1 , Ryo Nasuno 1 , Hiroshi Takagi 1
Affiliation  

The reduced form of nicotinamide adenine dinucleotide phosphate (NADPH), which is required for various redox systems involving antioxidative stress enzymes, is thus important for stress tolerance mechanisms. Here, we analyzed the stress response of the NADPH-depleted cells of Saccharomyces cerevisiae. A cell viability assay showed that the NADPH depletion induced by disruption of the ZWF1 gene encoding glucose-6-phosphate dehydrogenase, which is the major determinant of the intracellular NADPH/NADP+ ratio, enhanced the tolerance of S. cerevisiae to both oxidative and nitrosative stresses. The subsequent analyses demonstrated that the antioxidative transcriptional factor Yap1 was activated and the cytosolic catalase Ctt1, whose expression is regulated by Yap1, was upregulated in zwf1Δ cells irrespective of the presence or absence of stress stimuli. Moreover, deletion of the YAP1 or CTT1 gene inhibited the increased stress tolerance of zwf1Δ cells, indicating that Ctt1 dominantly contributed to the higher stress tolerance of zwf1Δ cells. Our findings suggest that an NADPH-independent mechanism enhances oxidative and nitrosative stress tolerance in ZWF1-lacking yeast cells.

中文翻译:

NADPH非依赖性机制增强缺乏葡萄糖6-磷酸脱氢酶活性的酵母细胞的氧化和亚硝化应激耐受性

烟酰胺腺嘌呤二核苷酸磷酸 (NADPH) 的还原形式是各种涉及抗氧化应激酶的氧化还原系统所必需的,因此对于应激耐受机制很重要。在这里,我们分析了 NADPH 耗尽的酿酒酵母细胞的应激反应。细胞活力测定表明,由编码葡萄糖-6-磷酸脱氢酶的ZWF1基因破坏诱导的 NADPH 耗竭,这是细胞内 NADPH/NADP +比率的主要决定因素,增强了酿酒酵母的耐受性氧化和亚硝化应激。随后的分析表明,抗氧化转录因子 Yap1 被激活,并且细胞溶质过氧化氢酶 Ctt1(其表达受 Yap1 调节)在zwf1 Δ 细胞中上调,无论是否存在应激刺激。此外,缺失YAP1CTT1基因抑制的增加的胁迫耐受zwf1 Δ细胞,表明CTT1显性促成的更高的胁迫耐受性zwf1 Δ细胞。我们的研究结果表明,NADPH 独立机制增强了缺乏ZWF1 的酵母细胞的氧化和亚硝化应激耐受性。
更新日期:2021-03-01
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